Cumulative prognostic value of p53 mutations and bcl-2 protein expression in head-and-neck cancer treated by radiotherapy

We investigated the prognostic significance of p53-gene mutation (exon 5-9) and bcl-2-protein expression in primary squamous-cell carcinoma of the hea d and neck (HNSCC) treated by curative radiotherapy (RT). Primary squamous- cell carcinomas for analysis were obtained from 85 consecutive head-and-nec k-cancer patients, with complete follow-up data. We detected bcl-2 protein in 24% (20/85) of HNSCC studied; 38 (45%) of the 85 tumours had cells beari ng p53 mutations. A strong association was observed between tobacco exposur e and bcl-2-protein expression (p = 0.003), an association also evident in those patients who had a p53-mutated carcinoma (p = 0.049). Moreover, we fo und that most of the bcl-2-positive cancers (70%) were also mutated in the p53 gene (p = 0.010). In univariate and in multivariate analyses, the simul taneous detection of bcl-2 expression and a p53-gene mutation in a tumour b iopsy specimen was associated with greater risk of locoregional failure (p = 0.002 and 0.001 respectively) and worse survival (p = 0.045 and 0.033) wi thin 5 years in HNSCC patients treated by RT, The present study shows a cum ulative prognostic value of simultaneous detection of bcl-2 over-expression and p53-gene aberration in some primary HNSCC treated with conventional RT , and provides further evidence for cross-talk between p53 and bcl-2, sugge sting that these genes are important determinants of radiation-induced apop tosis, thereby modulating resistance to RT. Int. J. Cancer (Pred. Oncol.) 8 4:573-579, 1999. (C) 1999 Wiley-Liss, Inc.